Allele Linked to Obesity in People

A single nucleotide polymorphism in BDNF is tied with lower levels of the protein and higher body-mass index.

Nov 3, 2015

Kerry Grens

FLICKR, TONY ALTERThe gene for brain-derived neurotropic factor (BDNF)—important for neuronal health and also implicated in appetite—has been associated with obesity in humans, and scientists have now figured out why. An allele of BDNF, called C, leads to lower protein levels because of disrupted binding to a transcription factor.

“Lower BDNF levels may contribute to obesity in people with the C allele. If these findings are supported by additional studies, boosting BDNF levels may prove beneficial,” lead author Joan Han of the University of Tennessee Health Science Center said in a press release.

Hans’s group combed through the genetic and health data of more than 31,000 people, finding that those with the C allele—caused by a single nucleotide polymorphism (SNP)—were more likely to have increased body fat and a higher body-mass index (BMI). The team also analyzed postmortem tissue from 84 people and found lower BDNF levels in the hypothalamus among those with the CC genotype.

In the lab, Hans and her colleagues found that a transcription factor binds to BDNF at the site on the typical allele where the SNP occurs. The SNP in the C allele reduces this binding, they showed last week (October 29) in Cell Reports.

“This study explains how a single genetic change in BDNF influences obesity and may affect BDNF protein levels. Finding people with specific causes of obesity may allow us to evaluate effective, more-personalized treatments,” study coauthor Jack Yanovski, an investigator at the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development, said in the press release.